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Plasma renin activity, plasma renin concentration and plasma angiotensin II were measured in 18 primigravid women and 17 multiparous women between 37 and 42 weeks of gestation. Seven of the primigravid and seven of the multiparous women were admitted to hospital because they developed hypertension during pregnancy. In the primigravid group, the mean angiotensin II level was significantly higher in the hypertensive than in the normotensive women. A highly significant correlation was found between diastolic blood pressure and plasma angiotensin II levels. Although a similar trend was seen in the multiparous women, there was a wide scatter of values and the relationship between diastolic blood pressure and plasma angiotensin II was not significant. No correlation could be established between plasma renin concentration and angiotensin II levels. However, there was a trend towards a negative correlation between plasma renin activity and plasma angiotensin II, suggesting that high angiotensin levels may suppress renal renin release. The influence of parturition on plasma angiotensin II levels was investigated in 12 women. Maternal plasma angiotensin II levels were significantly higher in the second stage of labor than in women delivered by elective cesarean section.

Digital filtering techniques can be applied to the recovery of the fetal electrocardiogram (ECG) from noise, using optimized digital filters matched to the frequency characteristics of the waveform. By forming a linear model of the fetal ECG, it is possible to measure time constants and characteristics on a real-time basis. The technique provides a powerful tool for the detection of subtle changes in the ECG, but the interpretation of these changes is critical to the application of the technique in fetal monitoring. Shifts in the ST segment and changes in T wave configuration are late indicators of fetal asphyxia, whereas the earliest indicators of stress are shortening of the PR interval and inversion of the normal positive relationship between the PR and RR intervals. The method appears to substantially enhance our ability to predict fetal stress at an early stage.

Amniotic fluid lecithin has been measured during the antenatal period and at comparable periods of gestation at the onset of spontaneous labour. Lecithin values were higher in labour, the difference being statistically significant in two of the three groups studied. Lecithin values were also measured serially during induced labour in 14 normal women at term. A significant fall was observed throughout labour. Creatinine levels were measured in the amniotic fluid in five of these patients and showed no significant change.

Twelve women in their first 3 months of pregnancy received an i.v. saline load (3 mmol sodium/kg) and a graded infusion of angiotensin II (Ang II; i.e. 4, 8 and 16 ng/kg per min). As controls, twelve comparable pregnant subjects received the saline infusion alone. Eight non-pregnant women underwent both protocols, with doses of 2, 4 and 8 ng/kg per min Ang II, and thus acted as their own controls. Saline loading evoked proportionately similar falls in basal plasma renin (PRC) and plasma aldosterone (PAC) concentrations in pregnant and non-pregnant women. Angiotensin II evoked a dose-dependent pressor response, a graded increase in PAC and a reduction in sodium and urate excretion in both pregnant and non-pregnant women. The administration of Ang II had a proportionately greater effect on sodium and urate excretion in non-pregnant than in pregnant women; the pressor response to Ang II was also decreased in the pregnant women. The stimulation of PAC by Ang II, however, did not differ between the two groups. These results show that refractoriness to the renal and vascular effects of Ang II is present as early as the eleventh week of gestation. They also support the hypothesis that there is a degree of dissociation between the renin-angiotensin system and PAC in normal pregnancy.

Twenty-five women with diagnoses of placenta previa on ultrasound examination underwent magnetic resonance imaging examination. An assessment of placental position and the relationship of the lower placental edge to the internal os was made with both techniques and the results were compared. There was complete correlation of placental localization but significant differences were found in the determination of the degree of placenta previa. This occurred more often with posteriorly situated placentas. Magnetic resonance imaging directly affected management with regard to delivery in seven cases. Magnetic resonance imaging provides a technique capable of accurately assessing placental position and its relationship to the cervix, thereby leading to a reduction in hospitalization and inappropriate operations.

1. An inhibitor of angiotensin-I-converting enzyme activity (D-3-mercapto-2-methylpropanoyl-L-proline, Captopril) was given to five chronically cannulated pregnant ewes and eleven rabbits in late pregnancy. 2. Within 2 min of administration to the sheep, Captopril had blocked the maternal conversion of angiotensin I to II, as assessed by the pressor response evoked by the i.v. administration of angiotensin I. Maternal and fetal basal systemic blood pressures had fallen within 10 min of administration. Although maternal systemic blood pressure returned to basal levels within 2 hr, fetal pressures remained low for up to 2 days. 3. All ewes went into spontaneous labour at or near term. One lamb was live-born but very weak and failed to establish suckling. The remaining seven lambs were fresh still-births. 4. Gestation length was significantly prolonged in the treated rabbits by comparison with ten controls. The still-birth rate was 37% in the treated animals and 6% in the controls (P less than 0.001). 5. It is concluded that the administration of Captopril to the two species studied is harmful to the fetus. The observations suggest that the drug rapidly crosses the placenta, and may cross the blood-brain barrier to exert a central effect. It may also interfere with the normal initiation of parturition.

The effects of labetalol were compared with those of placebo in a multicentre randomized double-blind and prospective study of 152 patients with mild to moderate, non-proteinuric pregnancy-induced hypertension. Labetalol in a dose of 100 mg three times daily, increasing to 200 mg three times daily where required, significantly reduced maternal mean arterial pressure. There was some reduction in preterm delivery, neonatal respiratory distress syndrome and jaundice in the labetalol-treated group. Intrauterine growth retardation and neonatal hypoglycaemia occurred with the same frequency in both groups. There were no perinatal deaths. Labetalol appears to be an effective agent in the management of mild to moderate pregnancy-induced hypertension. The data from this study suggest possible advantages and no apparent disadvantages for the fetus during its use.

A brush delivered to the biopsy site by a metal introducer and cannula set was tested as an alternative implement for transcervical collection of chorionic villi. This implement was easy to use and readily identified by ultrasound. With only one attempt at sampling, the overall collection rate for 83 patients was 65 per cent. With practice 84 per cent successful collection was achieved. Gestations between 8 and 11 weeks was the best time for collection of chorionic villi. A single sampling can produce adequate material (15 mg wet weight) suitable for diagnostic purposes. No gestation sac was perforated but some slight bleeding followed the procedure. Appreciable success following a single sampling attempt coupled with the low complication rate suggests that this technique may have clinical application and deserves further investigation.

Twenty-five women with primary carcinoma of the cervix were examined with magnetic resonance imaging (MRI). A number of different pulse sequences with T1 and T2 weighting were employed to determine optimum tissue contrast, and the potential for staging cervical cancer was assessed and compared with the clinical findings. MRI is seen to give a unique view of cervical cancer in particular in stage I and II disease where other imaging techniques have known limitations. In addition, stages III and IV were well seen with demonstration of tumour comparable with that of computerized axial tomography (CT).

Magnetic resonance imaging is a significant new imaging modality currently undergoing assessment. Already it has an established role in evaluation of the central nervous and musculoskeletal systems. Its potential application in gynaecology is reviewed with a discussion of its advantages over other imaging techniques.

Plasma angiotensin II was measured in the umbilical cord arterial and/or venous blood of 54 babies delivered vaginally and in 12 delivered by elective lower segment cesarean section. Angiotensin II was also measured in the peripheral venous blood of 51 of the mothers. Mean angiotensin II levels at delivery were higher in the cord venous blood of infants born to hypertensive than to normotensive mothers. Cord venous angiotensin II levels were always higher than those of the mother and there was a strongly positive relationship between maternal and fetal angiotensin II. The duration of the second stage of labor was found significantly to affect fetal angiotensin II levels, prolonged labor being associated with high levels. When this was taken into account, there was a highly significant positive relationship between the body weight of the infants and cord venous angiotensin II levels. There was an inverse relationship between cord venous pH and angiotensin II levels. Babies delivered by lower segment cesarean section had much lower angiotensin II levels than those delivered vaginally. The levels were, however, twice as high as those in the nonpregnant adult.

We assessed the ability of magnetic resonance, a recently introduced imaging technique, to demonstrate the maternal anatomy in obstetrics. The signal intensity of different maternal tissues using T1 and T2 weighted sequences was examined. The bony pelvis is depicted with sufficient clarity to provide an alternative to conventional X-ray pelvimetry. The placenta and cervix have a distinctive appearance facilitating the diagnosis of placenta praevia. The unique demonstration of cervical morphology will offer the potential for investigation into the ill-understood conditions of cervical dystocia and cervical incompetence.

Twelve women with stage I endometrial adenocarcinoma were examined by magnetic resonance imaging before definitive surgery. Using this technique the depth of myometrical invasion, tumour site and cervical involvement were assessed and the results compared with the operative and pathological findings. Magnetic resonance imaging is a unique non-invasive method of assessing the early stages of endometrial adenocarcinoma before radiotherapy and surgery.

Various fetal tissues with gestational ages that ranged from 6 to 22 weeks were cultured as explants, and the culture media were examined for the production of both active and acid-activated renin. Media from cultures of fetal kidney, both the male and female genital tracts, and umbilical cord vessels were found to contain large quantities of active and acid-activated renin. Consistent differences in the production patterns of renin were found between the tissues, which may reflect the different potentials of the tissues to produce renin in vivo.

Peripheral plasma concentrations of unconjugated oestradiol-17 beta, progesterone and total oestriol were measured in patients presenting with uncomplicated preterm labour. Control samples were obtained from normal healthy women matched for maternal age, parity and duration of pregnancy. Oestrogen concentrations were often higher and progesterone concentrations often lower in patients presenting in preterm labour, and in particular, in those presenting in advanced labour and those failing to respond to treatment with ritodrine, but the differences were not statistically significant.

A series of 4 separate studies were conducted to assess the incidence and short term consequence of bleeding associated with chorion villus sampling. Results support previous reports that risk of foetal-maternal transfusion as suggested by a rise in maternal serum alpha-fetoprotein (MSAFP) can occur. This occurrence is not consistent and need not be obvious even after therapeutic abortion. It is also transient and did not complicate mid-trimester neural tube screening or subsequent course of pregnancy. Eighty-seven percent of blood contaminating villus samples are of maternal origin. Following diagnosis 37% of patients reported some vaginal bleeding. This is mainly in the form of spotting which did not preclude normal pregnancy. Foetal loss occurred in 4 of the patients when bleeding considered heavier than spotting continued. In rhesus negative patients prophylactic anti-D gamma-globulin is advised, since neither Kleihauer counts nor MSAFP estimation reliably detect all foetal-maternal transfusions.

The renin-angiotensin system shows a marked increase in activity in normal pregnancy, with the major changes occurring in the first trimester. Evidence is presented to show that there is a physiologically inactive prorenin present in the plasma during pregnancy that achieves highest levels in the first half of pregnancy. The significance of this "acid-activated" renin has yet to be determined. Plasma angiotensin II levels are elevated throughout normal pregnancy, and a significant positive relationship has been established between maternal venous and cord venous levels at delivery. Recent studies on plasma AII levels in pregnancy hypertension have shown a positive correlation between diastolic blood pressure and plasma AII, and there is evidence that the high circulating levels of angiotensin may result in a feed-back suppression of renal renin release. Studies on the fetal circulation at delivery have also shown high levels of AII in the cord venous blood of infants born to mothers with pregnancy hypertension. Despite the increased level of activity of the renin-angiotensin system in normal pregnancy, sodium homeostasis is maintained. The possible reasons for the increased activity are discussed briefly.

The first recording of the fetal electrocardiogram was described 80 years ago. Since that time only the peak of the QRS complex has been used in fetal monitoring for the measurement of fetal heart rate. Attempts to quantify changes in the configuration and time constants have been attempted over the last 30 years but despite the data obtained from animal experiments suggesting configurational changes in relation to hypoxia, the problems of electrical noise and signal distortion have restricted the application of these observations in the detection of fetal hypoxia in the human. Recent technical developments have now enabled continuous real time monitoring of the PR interval, heart rate and ST segment, and their findings and the interrelationships between different variables suggest a new approach to precise monitoring of the fetal state.

The appearances of the amnion from two patients with polyhydramnios and two patients with oligohydramnios are described. In polyhydramnios the amnion showed a normal incidence of all the four patterns found in normal amnion at term and no abnormal features were noted. In oligohydramnios, two of four normal patterns predominated and intercellular canals were sparse.

Peripheral plasma concentrations of unconjugated oestradiol 17-beta, progesterone and total oestriol were measured in 21 patients presenting with 'uncomplicated' preterm labour. Serial measurements were made during intravenous treatment with ritodrine over a period of 24 h. Mean levels of unconjugated oestradiol 17-beta fell significantly during infusion with ritodrine. Changes in progesterone levels remained within the range of diurnal fluctuations normally found in uncomplicated late pregnancy. Mean total oestriol levels fell significantly, but the changes did not exceed normal variations. No correlation was found between the magnitude, the rate or the timing of changes in any of the hormones measured and the short or long term effects of ritodrine on uterine activity. Although alterations in the peripheral oestrogen concentrations may be a direct effect of beta-mimetics, it is unlikely that this mechanism is important in the inhibition of uterine activity.

The binding of tritiated angiotensin II to 20,000 x g particulate tractions of human placenta, chorion, and amnion was investigated. Binding to particles from the three tissues reached equilibrium within 10 minutes at 29 degrees C and was displaced by the addition of 1,000-fold excess of unlabeled angiotensin II. Scatchard analysis of the data showed that two classes of binding sites were present in the placental preparation. For the high-affinity site, values of 9 x 10(-9) M and 300 fmoles/mg of protein were obtained for the dissociation constant and the binding capacity, respectively. There was little specific binding in chorion and amnion.

Renin concentration was determined in plasma and amniotic fluid samples immediately after collection, after storage at -18 degrees C for up to 48 h, and after storage at 5 degrees C for as long as 48 h. Renin concentration increased, both in plasma (p less than 0.05) and amniotic fluid (P less than 0.02), after the storage at 5 degrees C, but no significant alteration occurred on storage at -18 degrees C. Partial activation of inactive renin could explain the observed increase in renin concentration at 5 degrees C.

In a prospective study the interactions between ACE and the renin-angiotensin system in 18 primigravid normotensive women were investigated throughout pregnancy. ACE activity was found to be depressed throughout pregnancy, rising in the last trimester and returning to non-pregnant values by 6 weeks post partum. No significant differences were found between cord arterial or venous and maternal venous ACE levels at delivery. ACE was inversely related to systolic and mean arterial blood pressures, inversely to serum sodium and urinary potassium and directly to serum potassium levels. Within the system, ACE was correlated only to aldosterone levels. In company with other components of the system ACE activity appears to be altered in pregnancy and to be influenced by similar control mechanisms. It is possible that ACE plays a modulating role on aldosterone secretion via the (des-asp1), Angiotensin I pathway.

Magnetic resonance imaging (MRI) was performed in 36 patients at between 10 and 38 weeks gestation to determine the fetal anatomy that could be identified at different gestations. Fetal motion significantly degraded the image quality in the first and second trimesters, but in the final trimester fetal anatomy was clearly demonstrated. T2 weighted sequences showed the fetal brain and lungs to have a high signal intensity. Shorter TR leading to a T1 weighting gave better resolution of the overall anatomy. MRI has revealed the potential for assessment of lung maturity and the growth-retarded fetus.

Changes in mood, plasma progesterone concentration, urinary volume, sodium excretion, sodium:potassium ratio, and body weight during the menstrual cycle were determined in 18 women with premenstrual syndrome and 10 symptomless (control group) women. Plasma progesterone concentration was higher in the women with symptoms during the postovulatory phase of the cycle, and the peak progesterone concentration appeared earlier. The changes in progesterone concentration were accompanied by a natriuresis and diuresis that fell towards preovulatory values in the premenstrual phase. Sodium retention was not confined to any definite period. Mood symptoms occurred after the changes in progesterone and electrolyte concentrations. Progesterone deficiency is probably not the cause of premenstrual syndrome. Thus treatment with progesterone is probably illogical unless a deficiency is detected. Treatment should be aimed at preventing the natriuretic effect of progesterone in the postovulatory phase and the sodium-retaining and water-retaining effects of aldosterone in the premenstrual phase.

Myometrium, decidua, chorio-decidua and amnion were collected from women undergoing caesarean section and from pregnant women at hysterectomy and hysterotomy for comparison with myometrium, cervix and endometrium taken from non-pregnant women at hysterectomy. Homogenates of chorio-decidua and amnion contained the largest concentrations of active and inactive renin. Cultured explants of all tissues except amnion were found to produce both types of renin. The percentage of active renin produced before 20 days of culture was significantly greater in cultures of chorio-decidua than in those of myometrium (P less than 0.0005) or decidua vera (P less than 0.025), which suggests that renin synthesis in vivo is probably confined to the chorio-decidua.

An outline is given of a computer-based system which continuously enhances and measures the waveform of the intrapartum fetal electrocardiogram. This system has been used to examine the behaviour of the ST segment and T wave in a group of 14 fetuses where the outcome was biochemically and clinically normal, and in a group of 10 fetuses which were acidotic at birth. When the mean values in each group were compared, highly significant differences were found for both of these components of the waveform. These differences have also been demonstrated by the analysis of long-term trends in the behaviour of these variables. The highly significant correlation between both a long-term increase in ST segment and T wave height and fetal acidosis, found in this study, reflects earlier work by others in the experimental animal fetus. The findings suggest that continuous monitoring of the waveform of the fetal electrocardiogram in labour may give a much better prediction of fetal acidosis than is currently achieved with the monitoring of heart rate alone.

One hundred twenty-three patients with suspected primary or recurrent gynecologic cancer were imaged after infusion with radiolabeled antitumor monoclonal antibody (791T/36). Overall sensitivity of tumor detection was 87% and specificity was 75%. Indium 111- and iodine 131-labeled antibody were compared, the former yielding a higher specificity for tumor detection. This antibody shows potential for routine tumor detection, particularly in cases of suspected recurrent cancer, but the development of antimouse antibodies is a drawback to this technique still to be overcome. The specific targeting of cytotoxic agents with this antibody is in progress.

302 women aged 16-80 without symptoms of spinal disease had their lumbar intervertebral discs examined by magnetic resonance. The prevalence of one or more degenerate discs increased linearly with age but disc degeneration was already present in over one-third of women aged 21-40; these young women may prove to be at special risk of disc prolapse later in life. The high prevalence of symptomless disc degeneration must be taken into account when magnetic resonance is used for assessment of spinal symptoms.

The surface morphology of normal term amnion was studied by scanning electron microscopy. Four patterns were observed. Two of the patterns showed distinctive minority populations of cells. In one, there were cells surrounded by intracellular channels; in the other, there were large flat cells. The microvilli in all four patterns showed variable morphology in different samples. Possible functional implications of the findings are discussed.

Serum prolactin was measured in 18 subjects complaining of premenstrual syndrome and results were compared with those in 10 control subjects. No consistent changes were seen during the course of the menstrual cycle in either group. There were no significant differences between the prolactin levels of the two groups. There was no correlation between mood change and levels of prolactin.

A composite titanium/silicone rubber clip has been developed for female sterilization. The 12.7 mm long metal clip is lined with silicone rubber and is bent round the Fallopian tube by means of an applicator that can be used laparoscopically. As tubal necorsis occurs, the rubber expands to keep the lumen blocked. The tube eventually divides and the stumps heal closed. Since the Mark 3 version of the clip was introduced, over 5700 women in several countries have been sterilized. The first 540 British women who were followed-up for five to 17 months experienced one method failure (ectopic) and tow operator failures, to total failure rate of 5.5/1000. Clip-related complications were minimal and long-term sequelae were comparable to tubal ligation. The clip causes minimal destruction but still seems effective for tubal occlusion and it can accommodate thick tubes.